Hypoxic preconditioning attenuates ischemia-reperfusion injury in young healthy adults.
Ischemic preconditioning attenuates the reduction in brachial artery endothelial function following an ischemia-reperfusion injury. Brief bouts of systemic hypoxemia could similarly mitigate the blunted vasodilatory response induced by an ischemia-reperfusion injury. The aim of the present study was to determine whether an acute bout of intermittent hypoxia protects against an ischemia-reperfusion injury in young healthy individuals. Brachial artery endothelial function was assessed by flow-mediated dilation in 16 young healthy individuals before and after a 20-min upper arm blood flow occlusion to induce ischemia-reperfusion injury. Blood flow occlusion was preceded by either intermittent hypoxia or intermittent normoxia. Intermittent hypoxia consisted of three 4-min hypoxic cycles at an arterial oxygen saturation of 87 ± 3% separated by 4-min normoxic cycles. Intermittent hypoxia resulted in a lower arterial oxygen saturation than intermittent normoxia (hypoxia: 87 ± 3% vs. normoxia: 99 ± 1%, P < 0.01), which was equivalent to a lower fraction of inspired oxygen (hypoxia: 0.123 ± 0.013 and normoxia: 0.210 ± 0.003, P < 0.01). When preceded by intermittent normoxia, blood flow occlusion resulted in a blunted flow-mediated dilation. In contrast, the reduction in flow-mediated dilation following blood flow occlusion was attenuated by prior exposure to intermittent hypoxia (hypoxia: 6.4 ± 1.9 to 4.4 ± 2.3% and normoxia: 7.1 ± 2.5 to 4.0 ± 2.4%, time × condition interaction P = 0.048). Exposure to intermittent hypoxia did not affect mean arterial pressure (hypoxia: 92 ± 9 mmHg and normoxia: 89 ± 8 mmHg, P = 0.19) or cardiac output (hypoxia: 5.8 ± 1.1 L·min-1 and normoxia: 5.3 ± 1.1 L·min-1, P = 0.29). In conclusion, hypoxic preconditioning attenuates the reduction in flow-mediated dilation induced by blood flow occlusion in young healthy individuals. Intermittent hypoxia represents a potential strategy to mitigate the effect of ischemia-reperfusion injury associated with ischemic events.NEW & NOTEWORTHY Ischemia-reperfusion injury induced by restoration of blood flow following occlusion impairs flow-mediated dilation, a marker of endothelium-dependent vasodilation. In young healthy adults, exposure to intermittent hypoxia, consisting of alternating short bouts of breathing hypoxic and normoxic air, before an ischemia-reperfusion injury significantly attenuated the reduction in flow-mediated dilation. Thus, hypoxic preconditioning represents a potential strategy to mitigate the effect of ischemia-reperfusion injury associated with ischemic events.


Managerial implications of calculating optimal nurse staffing in medical units.
A critical managerial decision in health care organizations is the staffing decision. We offer a model to derive an optimum mix of different staff categories that minimizes total cost subject to constraints imposed by the patient acuity system and minimum staffing policies in a medical unit of Fairbanks Memorial Hospital, Alaska. We also indicate several managerial implications on how our results and their sensitivity analyses can be used effectively in decision making in a variety of categories.


[Changes in the pattern of serum biliary acids and lipoprotein picture during therapy with biliary acids in cholesterol lithiasis].
Several studies are present in the literature about the efficacy of medical treatment with biliary acid, orally administered, on the symptomatic gallstone patients. Both this drugs act, with different mechanisms, on the same pathophysiological pathway, represented by the supersaturated bile in cholesterol. Aim of the present investigation was to study the possible modifications of serum bile acids pattern and of lipoproteins in a large sample of gallstone patients under long-term treatment with biliary acids. One hundred and twelve patients with radiolucent gallstones entered the study; 54 received chenodeoxycholic acid (CDCA) and 58 ursodeoxycholic (UDCA) at dosage of 15 mg/kg/daily. Blood samples for determination of serum cholesterol, triglycerides, phospholipids, lipoproteins, total and fractionated biliary acids were collected from each subjects every three months for a mean "follow-up" of 24 months. The levels of serum cholesterol, triglycerides and phospholipids showed a mild decrease only in the patients under therapy with CDCA, while no modifications were detected using UDCA. The same was found for two other parameters, HDL-cholesterol and lipoproteins, with both treatments during the overall period of follow-up. The biliary acids levels showed a significant increase only in the patients treated with CDCA, but no differences were found between "responders" and "non responders" to the therapy.


mHealth technology for ecological momentary assessment in physical activity research: a systematic review.
To systematically review the publications on ecological momentary assessment (EMA) relating to physical activity (PA) behavior in order to classify the methodologies, and to identify the main mHealth technology-based tools and procedures that have been applied during the first 10 years since the emergence of smartphones. As a result of this review, we want to ask if there is enough evidence to propose the use of the term "mEMA" (mobile-based EMA). A systematic review according to PRISMA Statement (PROSPERO registration: CRD42018088136). Four databases (PsycINFO, CINALH, Medline and Web of Science Core Collection) were searched electronically from 2008 to February 2018. A total of 76 studies from 297 potential articles on the use of EMA and PA were included in this review. It was found that 71% of studies specifically used "EMA" for assessing PA behaviors but the rest used other terminology that also adjusted to the inclusion criteria. Just over half (51.3%) of studies (39) used mHealth technology, mainly smartphones, for collecting EMA data. The majority (79.5%) of these studies (31 out of 39) were published during the last 4 years. On the other hand, 58.8% of studies that only used paper-and-pencil were published during the first 3 years of the 10-year period analyzed. An accelerometer was the main built-in sensor used for collecting PA behavior by means of mHealth (69%). Most of the studies were carried out on young-adult samples, with only three studies in older adults. Women were included in 60% of studies, and healthy people in 82%. The studies lasted between 1 and 7 days in 57.9%, and between three and seven assessments per day were carried out in 37%. The most popular topics evaluated together with PA were psychological state and social and environmental context. We have classified the EMA methodologies used for assessing PA behaviors. A total of 71% of studies used the term "EMA" and 51.3% used mHealth technology. Accelerometers have been the main built-in sensor used for collecting PA. The change of trend in the use of tools for EMA in PA coincides with the technological advances of the last decade due to the emergence of smartphones and mHealth technology. There is enough evidence to use the term mEMA when mHealth technology is being used for monitoring real-time lifestyle behaviors in natural situations. We define mEMA as the use of mobile computing and communication technologies for the EMA of health and lifestyle behaviors. It is clear that the use of mHealth is increasing, but there is still a lot to be gained from taking advantage of all the capabilities of this technology in order to apply EMA to PA behavior. Thus, mEMA methodology can help in the monitoring of healthy lifestyles under both subjective and objective perspectives. The tendency for future research should be the automatic recognition of the PA of the user without interrupting their behavior. The ecological information could be completed with voice messages, image captures or brief text selections on the touch screen made in real time, all managed through smartphone apps. This methodology could be extended when EMA combined with mHealth are used to evaluate other lifestyle behaviors.


The pattern of elderly abuse presenting to an emergency department.
To determine the pattern and frequency of elder abuse presenting to an urban Emergency unit in Singapore. The survey was conducted from May 1994 to December 1997. The patients consisted of adults who were 65 years or older who presented to the Emergency Department with non-accidental trauma or complained of other acts of cruelty. 17 cases of elder abuse were found, out of a total of 62,826 elderly patients. The frequency of elder abuse presenting to the Emergency Department was 0.03%. Elder abuse makes up 2.9% of all cases of family violence involving adults in this period. The average age was 74.6 years old. There was a predominance of Chinese females. In 58.8% the assailants were the daughter-in-law or son. 70.5% were ambulatory. Most (76.4%) had a chronic medical illness, commonly hypertension, diabetes mellitus, or both. Blunt musculoskeletal trauma, head or maxillofacial injuries were the commonest injuries encountered. Elder abuse is a significant subset of Family Violence. It may be more widespread than thought. Awareness of its occurrence is a first step in halting its progression.


Second-harmonic generation voltage imaging at subcellular resolution in rat hippocampal slices.
Action potential (AP) is a major signaling mechanism in the neuronal networks. Dendritic AP propagation is important for information processing within the individual neurons. Due to limitations of electrode-based techniques most research on subcellular AP propagation has been restricted to soma and proximal parts of the primary dendrites. Development of voltage-sensitive dyes (VSD) has opened up a possibility to measure voltage changes in the oblique dendrites and the spines. Membrane-bound organic VSD can be used both for fluorescent imaging and imaging of second-harmonic generation (SHG). Both phenomena are voltage dependent and can be used for measuring membrane potential changes. However, changes in SHG are linear to the change in the local membrane potential and its slope is constant across different compartments of cells. Although SHG demonstrates reasonable change with membrane voltage (over 10% per 100 mV), the signal-to-noise (S/N) ratio is currently lower in SHG measurement than in fluorescent methods.


Recent Advances in Laser-Induced Synthesis of MOF Derivatives.
Metal-organic frameworks (MOFs) are crystalline materials with permanent pores constructed by the self-assembly of organic ligands and metal clusters through coordination bonds. Due to their diversity and tunability, MOFs are used as precursors to be converted into other types of functional materials by pyrolytic recrystallization. Laser-induced synthesis is proven to be a powerful pyrolytic processing technique with fast and accurate laser irradiation, low loss, high efficiency, selectivity, and programmability, which endow MOF derivatives with new features. Laser-induced MOF derivatives exhibit high versatility in multidisciplinary research fields. In this review, first, the basic principles of laser smelting and the types of materials for laser preparation of MOF derivatives are briefly introduced. Subsequently, it is focused on the peculiarity of the engineering of structural defects and their applications in catalysis, environmental protection, and energy fields. Finally, the challenges and opportunities at the current stage are highlighted with the aim of elucidating the future direction of the rapidly growing field of laser-induced synthesis of MOF derivatives.


Hepatitis B virus DNA is enriched in polymorphonuclear leukocytes.
DNA hybridization and cell separation techniques were used to determine which blood components contained hepatitis B viral DNA sequences. Free monomer-length hepatitis B virus was found in large amounts in the polymorphonuclear leukocyte cell fraction in two of five HBsAG-positive patients. In these two patients, viral DNA sequences were not detected in the plasma or platelet fraction, whereas the mononuclear cell DNA contained small amounts of a 7.2 kb size unintegrated hepatitis B genome. These studies indicate that the major reservoir of unit-length viral DNA in the asymptomatic hepatitis B carriers studied here was in the polymorphonuclear leukocyte fraction. The basis for the presence of the viral DNA within these cells is presently unknown, but may relate to viral replication within, or phagocytosis of virus by, these cells.


Effect of growth temperature on the lipids of Pseudomonas fluorescens.
Pseudomonas fluorescens was grown in co ntinuous culture with glucose or NH4+ as the growth-limiting substrate. The total amount of lipid and the relative proportions of neutral lipid and phospholipid did not vary with the rate or temperature of growth. The amounts of the phospholipids, which were phosphatidyl glycerol, cardiolipin and phosphatidyl ethanolamine, altered with the type of growth limitation and with the temperature and rate of growth. A precise composition of phospholipid classes is not a requirement for growth at low temperature. Fatty acid composition also varied with changes of these growth conditions at temperatures above 10 degrees C, but at lower growth temperatures the degree of saturation of the lipids was strictly controlled, and was unaffected by changes in the growth rate or the nature of the growth-limiting substrate. The degree of saturation of the lipids was not critical at the higher growth temperatures, and the variation in the degree of saturation observed at these temperatures was due in part to a decreased ability of the organism to control the fatty acid composition of its lipids at temperatures above 10 degrees C.


Efficient detection of occlusion prior to robust face recognition.
While there has been an enormous amount of research on face recognition under pose/illumination/expression changes and image degradations, problems caused by occlusions attracted relatively less attention. Facial occlusions, due, for example, to sunglasses, hat/cap, scarf, and beard, can significantly deteriorate performances of face recognition systems in uncontrolled environments such as video surveillance. The goal of this paper is to explore face recognition in the presence of partial occlusions, with emphasis on real-world scenarios (e.g., sunglasses and scarf). In this paper, we propose an efficient approach which consists of first analysing the presence of potential occlusion on a face and then conducting face recognition on the nonoccluded facial regions based on selective local Gabor binary patterns. Experiments demonstrate that the proposed method outperforms the state-of-the-art works including KLD-LGBPHS, S-LNMF, OA-LBP, and RSC. Furthermore, performances of the proposed approach are evaluated under illumination and extreme facial expression changes provide also significant results.


Resource Recovery from Wastewater by Biological Technologies: Opportunities, Challenges, and Prospects.
Limits in resource availability are driving a change in current societal production systems, changing the focus from residues treatment, such as wastewater treatment, toward resource recovery. Biotechnological processes offer an economic and versatile way to concentrate and transform resources from waste/wastewater into valuable products, which is a prerequisite for the technological development of a cradle-to-cradle bio-based economy. This review identifies emerging technologies that enable resource recovery across the wastewater treatment cycle. As such, bioenergy in the form of biohydrogen (by photo and dark fermentation processes) and biogas (during anaerobic digestion processes) have been classic targets, whereby, direct transformation of lipidic biomass into biodiesel also gained attention. This concept is similar to previous biofuel concepts, but more sustainable, as third generation biofuels and other resources can be produced from waste biomass. The production of high value biopolymers (e.g., for bioplastics manufacturing) from organic acids, hydrogen, and methane is another option for carbon recovery. The recovery of carbon and nutrients can be achieved by organic fertilizer production, or single cell protein generation (depending on the source) which may be utilized as feed, feed additives, next generation fertilizers, or even as probiotics. Additionlly, chemical oxidation-reduction and bioelectrochemical systems can recover inorganics or synthesize organic products beyond the natural microbial metabolism. Anticipating the next generation of wastewater treatment plants driven by biological recovery technologies, this review is focused on the generation and re-synthesis of energetic resources and key resources to be recycled as raw materials in a cradle-to-cradle economy concept.


Combined Association of Cardiorespiratory Fitness and Body Fatness With Cardiometabolic Risk Factors in Older Norwegian Adults: The Generation 100 Study.
To investigate the independent and combined associations of fitness and fatness with cardiometabolic risk factors in older Norwegian women and men. We conducted a cross-sectional study of 505 women and 417 men aged 70 to 77 years enrolled in the Generation 100 study in Norway. Fitness was assessed as peak oxygen uptake and fatness as high body mass index (BMI; ≥25 kg/m2), waist circumference (WC) of 88 cm or greater for women and 102 cm or greater for men, and percent body fat (%BF) of 35% or greater and 25% or greater for women and men, respectively. High cardiometabolic risk was defined as the presence of 2 or more of the following risk factors: elevated triglyceride level, reduced high-density lipoprotein cholesterol concentration, elevated blood pressure, and elevated fasting glucose level or pharmacological treatment of these conditions. Receiver operating characteristic curve analyses identified fitness levels of less than 25.7 and less than 30.7 mL/kg per minute in women and men, respectively, as critical thresholds for having high cardiometabolic risk. Individuals with levels below these thresholds had an adjusted odds ratio of 2.77 (95% CI, 2.09-3.66) for having high cardiometabolic risk, while high BMI, WC, and %BF had odds ratios (95% CIs) of 3.58 (2.69-4.77), 3.06 (2.29-4.10), and 3.26 (2.47-4.30), respectively. In our combined analyses, being lean did not attenuate the cardiometabolic risk associated with low fitness, and combinations of low fitness and/or high BMI, WC, or %BF cumulatively increased cardiometabolic risk. Low fitness and indication of fatness were independently and cumulatively associated with poor cardiometabolic health. Our results emphasize the importance of including both physical fitness and body fatness in the assessment of cardiometabolic risk and health promotion efforts in older adults.


The effect of immunodeficiency on cutaneous delayed-type hypersensitivity testing in HIV-infected women without anergy: implications for tuberculin testing. HER Study Group. HIV Epidemiology Research.
A collaborative study in four urban medical centers in the United States. To determine the effect of human immunodeficiency virus (HIV) infection and immunodeficiency on delayed type hypersensitivity (DTH) responses and the implications for interpretation of tuberculin reactions in non-anergic women with or at risk for HIV infection. Demographic and behavioral information, HIV antibody testing, CD4+ lymphocyte counts, and cutaneous responses to DTH testing with mumps, Candida, tetanus toxoid, and tuberculin (purified protein derivative-PPD) antigens were obtained in 1184 women. Reactions to one or more of the four antigens occurred in 436 HIV-seropositive and 356 high-risk seronegative women. Among non-anergic women, HIV-seropositives were less likely (P < or = 0.05) to react to mumps (62% vs 81%), tetanus (72% vs 84%), and PPD (13% vs 19%). Induration in HIV-seropositive reactors was associated with CD4+ cell level for mumps (P = 0.004) and tetanus (P < 0.001), but not for Candida or PPD. HIV-seropositive reactors with CD4+ cell counts >500/mm3 did not have significantly smaller reactions than HIV-seronegatives for any antigen tested. PPD sizes were similar among HIV-seropositive reactors with CD4+ cell counts >500/mm3 (12.4 +/- 7.4 mm) and HIV-seronegative reactors (12.0 +/- 8.3 mm); induration > or =10 mm was seen in 16/173 (9.2%) seropositive women with CD4+ cell counts >500/mm3 and 41/356 (11.5%) seronegative women, respectively (P = 0.5). Among HIV-infected women able to react to a DTH antigen, induration in response to that antigen was relatively intact at CD4+ counts >500/mm3. This suggests that degree of immunodeficiency should be considered when interpreting PPD reactions in HIV-infected persons.


Medical evacuations in the oil and gas industry: a retrospective review with implications for future evacuation and preventative strategies.
Businesses increasingly conduct operations in remote areas where medical evacuation [Medevac(s)] carries more risk. Royal Dutch Shell developed a remote healthcare strategy whereby enhanced remote healthcare is made available to the patient through use of telemedicine and telemetry. To evaluate that strategy, a review of Medevacs of Shell International employees [i.e. expatriate employees (EEs) and frequent business travellers (FBTs)] was undertaken. A retrospective review of Medevac data (period 2008-12) that were similar in operational constraints and population profile was conducted. Employee records and Human Resource data were used as a denominator for the population. Analogous Medevac data from specific locations were used to compare patterns of diagnoses. A total of 130 Medevacs were conducted during the study period, resulting in a Medevac rate of 4 per 1000 of population with 16 per 1000 for females and 3 per 1000 for males, respectively. The youngest and oldest age-groups required Medevacs in larger proportions. The evacuation rates were highest for countries classified as 'high' or 'extreme risk'. The most frequent diagnostic categories for Medevac were: trauma, digestive, musculoskeletal, cardiac and neurological. In 9% of the total, a strong to moderate link could be made between the pre-existing medical condition and diagnosis leading to Medevac. This study uniquely provides a benchmark Medevac rate (4 per 1000) for EEs and FBTs and demonstrates that Medevac rates are highest from countries identified as 'high risk'; there is an age and gender bias, and pre-existing medical conditions are of notable relevance. It confirms a change in the trend from injury to illness as a reason for Medevac in the oil and gas industry and demonstrates that diagnoses of a digestive and traumatic nature are the most frequent. A holistic approach to health (as opposed to a predominant focus on fitness to work), more attention to female travellers, and the application of modern technology and communication will reduce the need for Medevacs.


Identifying Patients with Polycythemia Vera at Risk of Thrombosis after Hydroxyurea Initiation: The Polycythemia Vera-Advanced Integrated Models (PV-AIM) Project.
Patients with polycythemia vera (PV) are at significant risk of thromboembolic events (TE). The PV-AIM study used the Optum® de-identified Electronic Health Record dataset and machine learning to identify markers of TE in a real-world population. Data for 82,960 patients with PV were extracted: 3852 patients were treated with hydroxyurea (HU) only, while 130 patients were treated with HU and then changed to ruxolitinib (HU-ruxolitinib). For HU-alone patients, the annualized incidence rates (IR; per 100 patients) decreased from 8.7 (before HU) to 5.6 (during HU) but increased markedly to 10.5 (continuing HU). Whereas for HU-ruxolitinib patients, the IR decreased from 10.8 (before HU) to 8.4 (during HU) and was maintained at 8.3 (after switching to ruxolitinib). To better understand markers associated with TE risk, we built a machine-learning model for HU-alone patients and validated it using an independent dataset. The model identified lymphocyte percentage (LYP), neutrophil percentage (NEP), and red cell distribution width (RDW) as key markers of TE risk, and optimal thresholds for these markers were established, from which a decision tree was derived. Using these widely used laboratory markers, the decision tree could be used to identify patients at high risk for TE, facilitate treatment decisions, and optimize patient management.


Evidence for age-dependent impairment of ovalbumin heterogeneous nuclear RNA (HnRNA) processing in hen oviduct.
The expression of the ovalbumin gene in hen oviduct decreases during ageing. Northern transfer of electrophoretically fractionated total RNA from oviducts of mature egg-laying and old non-egg-laying hens, and hybridization to nick-translated plasmid pOV230 (ovalbumin complementary DNA cloned into pMB9) revealed with age increasing concentrations of distinct high-molecular-weight ovalbumin pre-mRNA species as compared with that of functional 18S ovalbumin mRNA. The accumulation of ovalbumin sequence-containing processing intermediates in old hen oviducts indicates lowered rates of RNA splicing and/or altered steady state concentrations of splicing intermediates during post-transcriptional maturation of heterogeneous nuclear RNA in old animals.


Direct detection of small molecules using a nano-molecular imprinted polymer receptor and a quartz crystal resonator driven at a fixed frequency and amplitude.
Small molecule detection is of wide interest in clinical and industrial applications. However, its accessibility is still limited as miniaturisation and system integration is challenged in reliability, costs and complexity. Here we combined a 14.3 MHz quartz crystal resonator (QCR), actuated and analysed using a fixed frequency drive (FFD) method, with a nanomolecular imprinted polymer for label-free, realtime detection of N-hexanoyl-L-homoserine lactone (199 Da), a gram-negative bacterial infection biomarker. The lowest concentration detected (1 μM) without any optimisation was comparable with that of a BIAcore SPR system, an expensive laboratory gold standard, with significant enhancement in sensitivity and specificity beyond the state-of-the-art QCR. The analytical formula-based FFD method can potentially allow a multiplexed "QCR-on-chip" technology, bringing a paradigm shift in speed, accessibility and affordability of small molecule detection.


[The physiological significance of proliferative and alterative processes].
This article is a brief review of publications dedicated to a problem of basic regularities of proliferative and alternative processes in health and disease and their physiological, general biological and special meaning. Historical background shows the evolution of scientists' viewpoints regarding essentials and reasons of diseases. The publication spotlights systematization of proliferative and alternative reactions in different pathophysiological processes. It is underlined that the development of morbid conditions can start not only with structural-functional changes, but also with failure of physiological processes of regulation. A principle of universality and balance of cell and humeral responses is taken as a basis of humoral-cell proliferation, which is provided, on one side by their conservatism and on the other side by their flexibility. Modern investigations confirm that various physiological reactions of proliferation in organism are allelically determined more frequently, and their disturbances may have epigenetic character. The main physiological meaning of proliferative and destructive processes remains their protective-adaptive role in organism, and their study and diagnostics keep an important section in recognition of various pathophysiological states.


The interaction-induced dipole of H2-H: New ab initio results and spherical tensor analysis.
We present numerical results for the dipole induced by interactions between a hydrogen molecule and a hydrogen atom, obtained from finite-field calculations in an aug-cc-pV5Z basis at the unrestricted coupled-cluster level including all single and double excitations in the exponential operator applied to a restricted Hartree-Fock reference state, with the triple excitations treated perturbatively, i.e., UCCSD(T) level. The Cartesian components of the dipole have been computed for nine different bond lengths r of H2 ranging from 0.942 a.u. to 2.801 a.u., for 16 different separations R between the centers of mass of H2 and H between 3.0 a.u. and 10.0 a.u., and for 19 angles θ between the H2 bond vector r and the vector R from the H2 center of mass to the nucleus of the H atom, ranging from 0° to 90° in intervals of 5°. We have expanded the interaction-induced dipole as a series in the spherical harmonics of the orientation angles of the H2 bond axis and of the intermolecular vector, with coefficients DλL(r, R). For the geometrical configurations that we have studied in this work, the most important coefficients DλL(r, R) in the series expansion are D01(r, R), D21(r, R), D23(r, R), D43(r, R), and D45(r, R). We show that the ab initio results for D23(r, R) and D45(r, R) converge to the classical induction forms at large R. The convergence of D45(r, R) to the hexadecapolar induction form is demonstrated for the first time. Close agreement between the long-range ab initio values of D01(r0 = 1.449 a.u., R) and the known analytical values due to van der Waals dispersion and back induction is also demonstrated for the first time. At shorter range, D01(r, R) characterizes isotropic overlap and exchange effects, as well as dispersion. The coefficients D21(r, R) and D43(r, R) represent anisotropic overlap effects. Our results for the DλL(r, R) coefficients are useful for calculations of the line shapes for collision-induced absorption and collision-induced emission in the infrared and far-infrared by gas mixtures containing both H2 molecules and H atoms.


Electroencephalogram (EEG) in the management of epilepsy in children.
Electroencephalogram (EEG) has an important role in the management of seizure disorder in children. It helps in diagnosis and classification of epilepsy, choosing of antiepileptic medication and prediction of prognosis. When history of epilepsy is unclear, EEG can help to distinguish epileptiform discharges from its counterpart. But EEG has limitations. In epilepsy, EEG has variable range of sensitivity and specificity. Hereby, during interpretation of EEG, clinical situation should not be ignored. Interictal EEG has important diagnostic and prognostic value in epilepsy. But caution is needed during evaluation of significance of interictal epileptiform discharge (IED). Methods like recording of EEG in awake and sleep state, hyperventilation and photic stimulation enhances the yield of interictal EEG. Long term EEG recording has an important role in the assessment of patients who present diagnostic or management difficulties following clinical evaluation and routine EEG.


Workstation scheme and implementation for a medical imaging information system.
To discuss the scheme and implementation of workstation configuration for medical imaging information systems suitable to the practical situation in China. The workstations were logically divided into picture archiving and communication system (PACS) workstations and radiology information system (RIS) workstations. The former applied to three kinds of diagnostic practice: the small matrix images, large matrix images and high resolution grayscale display applications. The latter consisted many different models defined by the usage and function processes. A dual-screen configuration for image interpretation workstations integrated the image-viewing and reporting procedures physically. Small matrix images as CT or MR were operated on 17 inch (1 inch = 2.54 cm) color monitors, while conventional X-ray interpretation was performed on 21 inch color monitors or portrait format grayscale 2 k by 2.5 k monitors. All other RIS workstations not involved in imaging process were set up with a common PC configuration. Workstation schemes for medical imaging information systems should satisfy the basic requirements of medical imaging and investment budget.


Transient depression of myocardial function after influenza virus infection: A study of echocardiographic tissue imaging.
Influenza virus infection (IVI) was reported to be associated with minor cardiac changes, mostly those detected on electrocardiogram with and without elevated blood markers of myocardial injury; however, the characteristics of myocardial involvement in association with IVI are poorly understood. This study used echocardiographic tissue imaging (tissue Doppler, strain, and strain rate) to evaluate changes in left atrial (LA) and left ventricular (LV) myocardial function after IVI. We examined 20 adult individuals (mean age, 43 years) at 2 and 4 weeks after diagnosis of IVI. For myocardial functional variables, we obtained LV global longitudinal strain (GLS), LV early diastolic strain rate (e'sr), LA strain, and LA stiffness (E/e'/LA strain), in addition to data on tissue Doppler (s', e', and a') and myocardial performance index. Blood markers of myocardial injury were also examined. During follow-up, there were no significant changes in global chamber function such as LV ejection fraction, E/e', and LA volume. However, significant changes in myocardial function were observed, namely, in s' (8.0 ± 1.6 cm/s to 9.3 ± 1.5 cm/s; p = 0.01), e' (10.2 ± 2.8 cm/s to 11.4 ± 3.0 cm/s; p < 0.001), e'sr (1.43 ± 0.44 1/s to 1.59 ± 0.43 1/s; p = 0.005), and LA strain (35 ± 8% to 40 ± 12%; p = 0.025), and the myocardial performance index (0.52 ± 0.20 to 0.38 ± 0.09; p = 0.009), but not in a', LA stiffness, or GLS. Cardiac troponin T and creatinine kinase isoenzyme MB were not elevated significantly at any examination. Myocardial dysfunction during IVI recovery appeared to be transient particularly in the absence of myocardial injury. Echocardiographic tissue imaging may be useful to detect subclinical cardiac changes in association with IVI.


Inhibition of calcium release of diazoxide studied in the isolated rat kidney.
Isolated kidneys of normotensive Wistar rats (NWR) and of genetically hypertensive Kyoto rats (SHR) were perfused. Contraction of intrarenal vascular smooth muscle cells were induced by barium ions (0.1 to 1.0 mmol) as well as by high potassium concentrations (40 mmol). It was shown that barium stimulates intracellular calcium stores to release activator calcium. Repeated stimulation with barium under calcium-free perfusion conditions resulted in depletion of these stores. In kidneys of SHR rats the tension development in response to barium was stronger as compared with NWR rats and the time needed to deplete the stores was prolonged. This suggests that smooth muscle cells of SHR rats contain more sequestered calcium. Diazoxide inhibited the barium contracture rapidly, reversibly and dose dependently. The inhibition was non-competitive. Percentual inhibition was equal in NWR and in SHR rat kidneys. Moreover, diazoxide did not block the calcium influx across the sarcolemma membrane. The magnitude of the potassium contractures depended entirely upon the extracellular calcium concentration. In the range of 0.1 to 1.0 mmol calcium, tension development varied linearly with log calcium concentration. Diazoxide also inhibited the potassium contractures, provided normally filled calcium stores were available. The combined results strongly suggest that diazoxide prevents intracellular calcium stores to release calcium and, furthermore, that this action is the basic mechanism of the vasodilating activity of diazoxide in smooth muscle cells of rat intrarenal vessels.


The lower quality of preventive care among forced migrants in a country with universal healthcare coverage.
To assess the association between socio-demographic factors and the quality of preventive care and chronic care of cardiovascular (CV) risk factors in a country with universal health care coverage. Our retrospective cohort assessed a random sample of 966 patients aged 50-80years followed over 2years (2005-2006) in 4 Swiss university primary care settings (Basel/Geneva/Lausanne/Zürich). We used RAND's Quality Assessment Tools indicators and examined recommended preventive care among different socio-demographic subgroups. Overall patients received 69.6% of recommended preventive care. Preventive care indicators were more likely to be met among men (72.8% vs. 65.4%; p<0.001), younger patients (from 71.0% at 50-59years to 66.7% at 70-80years, p for trend=0.03) and Swiss patients (71.1% vs. 62.7% in forced migrants; p=0.001). This latter difference remained in multivariate analysis adjusted for gender, age, civil status and occupation (OR 0.68; 95% CI 0.54-0.86). Forced migrants had lower scores for physical examination and breast and colon cancer screening (all p≤0.02). No major differences were seen for chronic care of CV risk factors. Despite universal healthcare coverage, forced migrants receive less preventive care than Swiss patients in university primary care settings. Greater attention should be paid to forced migrants for preventive care.


Mutualism breakdown by amplification of Wolbachia genes.
Most insect species are associated with vertically transmitted endosymbionts. Because of the mode of transmission, the fitness of these symbionts is dependent on the fitness of the hosts. Therefore, these endosymbionts need to control their proliferation in order to minimize their cost for the host. The genetic bases and mechanisms of this regulation remain largely undetermined. The maternally inherited bacteria of the genus Wolbachia are the most common endosymbionts of insects, providing some of them with fitness benefits. In Drosophila melanogaster, Wolbachia wMelPop is a unique virulent variant that proliferates massively in the hosts and shortens their lifespan. The genetic bases of wMelPop virulence are unknown, and their identification would allow a better understanding of how Wolbachia levels are regulated. Here we show that amplification of a region containing eight Wolbachia genes, called Octomom, is responsible for wMelPop virulence. Using Drosophila lines selected for carrying Wolbachia with different Octomom copy numbers, we demonstrate that the number of Octomom copies determines Wolbachia titers and the strength of the lethal phenotype. Octomom amplification is unstable, and reversion of copy number to one reverts all the phenotypes. Our results provide a link between genotype and phenotype in Wolbachia and identify a genomic region regulating Wolbachia proliferation. We also prove that these bacteria can evolve rapidly. Rapid evolution by changes in gene copy number may be common in endosymbionts with a high number of mobile elements and other repeated regions. Understanding wMelPop pathogenicity and variability also allows researchers to better control and predict the outcome of releasing mosquitoes transinfected with this variant to block human vector-borne diseases. Our results show that transition from a mutualist to a pathogen may occur because of a single genomic change in the endosymbiont. This implies that there must be constant selection on endosymbionts to control their densities.


LDH concentration in nasal-wash fluid as a biochemical predictor of bronchiolitis severity.
Because the decision to hospitalize an infant with bronchiolitis is often supported by subjective criteria and objective indicators of bronchiolitis severity are lacking, we tested the hypothesis that lactate dehydrogenase (LDH), which is released from injured cells, is a useful biochemical indicator of bronchiolitis severity. We retrospectively analyzed a study of children <24 months old presenting to the emergency department with bronchiolitis. Demographic, clinical information, nasal wash (NW), and serum specimens were obtained. NW samples were analyzed for respiratory viruses, caspase 3/7 activity, and a panel of cytokines and chemokines. Total LDH activity was tested in NW samples and sera. Of 101 enrolled children (median age: 5.6 months), 98 had NW specimens available. A viral etiology was found for 82 patients (83.6%), with respiratory syncytial virus (RSV) (66%) and rhinovirus (19%) being the most common viruses detected. Concentrations of LDH in NW specimens were independent from those in sera and were higher in children with RSV infection or with dual infection. Significant correlations were found between NW LDH and NW cytokines/chemokines. Similarly, NW LDH correlated with NW-caspase 3/7 activity (r = 0.75; P < .001). In a multivariate analysis, NW LDH concentration in the upper quartile was significantly associated with a reduced risk of hospitalization (odds ratio: 0.19 [95% confidence interval: 0.05-0.68]; P = .011). NW LDH levels in young children with bronchiolitis varied according to viral etiology and disease severity. Values in the upper quartile were associated with approximately 80% risk reduction in hospitalization, likely reflecting a robust antiviral response. NW LDH may be a useful biomarker to assist the clinician in the decision to hospitalize a child with bronchiolitis.


Peripheral nerve blocks for lower limb surgery--a choice anaesthetic technique for patients with a recent myocardial infarction?
Peripheral nerve blocks are associated with minimal haemodynamic disturbance. It is perhaps ideal for high-risk surgical patients who cannot tolerate the adverse consequences of even the slightest attenuation of haemodynamic response. However, peripheral nerve blockade is often perceived to be time consuming and undependable as the sole anaesthetic. In this report, a 56-year-old man with severe sepsis and recent myocardial infarction presents for an urgent above knee amputation. We present the practical benefits of a combined sciatic-femoral nerve block on such a patient.


E3 Ubiquitin Ligases as Immunotherapeutic Target in Atherosclerotic Cardiovascular Disease.
Chronic low-grade inflammation drives atherosclerosis and despite optimal pharmacological treatment of classical cardiovascular risk factors, one third of the patients with atherosclerotic cardiovascular disease has elevated inflammatory biomarkers. Additional anti-inflammatory strategies to target this residual inflammatory cardiovascular risk are therefore required. T-cells are a dominant cell type in human atherosclerotic lesions. Modulation of T-cell activation is therefore a potential strategy to target inflammation in atherosclerosis. Ubiquitination is an important regulatory mechanism of T-cell activation and several E3 ubiquitin ligases, including casitas B-lineage lymphoma proto-oncogene B (Cbl-B), itchy homolog (Itch), and gene related to anergy in lymphocytes (GRAIL), function as a natural brake on T-cell activation. In this review we discuss recent insights on the role of Cbl-B, Itch, and GRAIL in atherosclerosis and explore the therapeutic potential of these E3 ubiquitin ligases in cardiovascular medicine.


Trends in recreational computer use among Latino children in California.
In this study we examine differential trends in recreational computer use among Latino and white children in California. We analyzed data from the children's sample (age 4-11) of the 2001 and 2009 California Health Interview Survey. Multivariate analysis was used to estimate the impact of language spoken at home, income and parental education, on recreational computer use. Latino children had substantially lower recreational computer use in 2001, compared to whites, but by 2009 the gap had almost disappeared. Among Latinos, compared to families where English is spoken exclusively, recreational computer use was substantially lower in families where Spanish is spoken exclusively. Parental education and income were significantly associated with recreational computer use, but only among Latinos, and the association with parental education changed from 2001 to 2009, explaining some of the difference in trend between Latino and white children.


Expression of the Lyst(beige) mutation is atheroprotective in chow-fed apolipoprotein E-deficient mice.
Lyst(beige) mice crossed with hyperlipidemic low density lipoprotein receptor-deficient mice (BgLDLr(-/-)) display increased lesion area and a more stable lesion morphology. To verify that the beige phenotype is not unique to LDLr(-/-) mice, we examined atherosclerosis in beige, apolipoprotein E-deficient mutant mice (BgApoE(-/-)). Severe diet-induced hyperlipidemia in BgApoE(-/-) mice resulted in increased aortic sinus lesion areas compared with controls. Minimal aortic lesions were observed in both genotypes on a chow diet. Nevertheless, BgApoE(-/-) mice displayed drastically reduced aortic sinus lesion growth. Reconstitution with bone marrow (BM) from green fluorescent protein mice created chimeric animals that allowed for the identification of donor-derived cells within lesions. Expressing the beige mutation exclusively in BM-derived cells had no impact on plaque development, yet the beige mutation in all cells except the BM-derived cells led to significantly larger aortic sinus lesion areas. Both mRNA and secreted protein levels of monocyte chemoattractant protein 1 were altered in quiescent and phorbol ester-stimulated cultured macrophages, vascular smooth muscle cells, and aortic endothelial cells isolated from BgApoE(-/-) mice. Thus, expression of the beige mutation in all cell types involved in lesion development contributed to atheroprotection in chow-fed ApoE(-/-) mice.


Pseudo complications of cardiac catheterization: update.
This prospective study was performed to determine whether complications that occur immediately before or after the time of scheduled catheterization are as much disease-related as procedure-related. During 24 months all complications associated with 1,606 diagnostic cardiac catheterizations were recorded if they occurred from 24 hours before the time the procedure was scheduled to 72 hours later, longer if complications were clearly procedure-related. Pseudo complications are spontaneous medical or surgical incidents that occur during the 24-hour period before catheterization is scheduled to be performed. Procedure-related complications are incidents that occur during or after the catheterization procedure. There were 13 (0.81%) procedure-related complications but not deaths. There were 13 (0.81%) pseudo complications including 4 (0.24%) deaths. All complications were similar in nature except for 3 instances of vascular injury, which were procedure-related. Pseudo complications occur as commonly as procedure-related complications and at times are more severe. Complications occurring before catheterization are related to the underlying disease process and not medical intervention. It is likely that similar disease-caused incidents occur after a catheterization and are not necessarily procedure-related.


The prescribing pattern of hospital doctors.
There has been no local data on the prescribing habits of doctors over the last 25 years. This is a retrospective study done to examine the outpatient prescribing pattern of doctors at Alexandra Hospital over a one month period in 1995. Six-thousand five-hundred and three scripts were analysed. A total of 16,642 items were prescribed. The distribution of prescription scripts by departments included Accident & Emergency 39.0%; Medical 23.5%; Orthopaedics 10.3%; Surgery 18.5%; Paediatrics 4.4%, and Geriatrics 4.3%. The overall mean number of drugs prescribed was 2.6 (median = 2, mode = 2, range = 14). Analysis of the overall results by age groups showed the following means for "total number of drugs prescribed": (> 0 to 20 years) = 2.23, (> 20 to 40 years) = 2.42, (> 40 to 60 years) = 2.61 and (> 60 years) = 3.18. Analysis of variance showed highly significant results between the means of each age-group. Post-hoc analysis revealed that the oldest age group (> 60 years) accounted for most of this significant result. The top 10 drugs used by the hospital were (in descending order): NSAIDs, antacids, analgesics (other than NSAID), antibiotics, topical medications, anti-diarrhoeal agents, anti-histamines, vitamins, anti-emetics and promethazine cough syrup. There was a high usage of NSAID-antacid combination. Similarly, amoxycillin was often given with cloxacillin. There was an underuse of anti-depressants. There were very few (0.15%) illegible prescriptions. Only one prescription had an adverse combination of drugs. This is the first local study of prescribing pattern of a hospital. While this data may vary from hospital to hospital, depending on the patient mix, it does provide some useful baseline data which hitherto never existed. Our findings suggested that the elderly do receive more medications.


Investigating the utility of traditional and genomic multi-locus datasets to resolve relationships in Lipaugus and Tijuca (Cotingidae).
Rapid diversification limits our ability to resolve evolutionary relationships and examine diversification history, as in the case of the Neotropical cotingas. Here we present an analysis with complete taxon sampling for the cotinga genera Lipaugus and Tijuca, which include some of the most range-restricted (e.g., T. condita) and also the most widespread and familiar (e.g., L. vociferans) forest birds in the Neotropics. We used two datasets: (1) Sanger sequencing data sampled from eight loci in 34 individuals across all described taxa and (2) sequence capture data linked to 1,079 ultraconserved elements and conserved exons sampled from one or two individuals per species. Phylogenies estimated from the Sanger sequencing data failed to resolve three nodes, but the sequence capture data produced a well-supported tree. Lipaugus and Tijuca formed a single, highly supported clade, but Tijuca species were not sister and were embedded within Lipaugus. A dated phylogeny confirmed Lipaugus and Tijuca diversified rapidly in the Miocene. Our study provides a detailed evolutionary hypothesis for Lipaugus and Tijuca and demonstrates that increasing genomic sampling can prove instrumental in resolving the evolutionary history of recent radiations.


A fatal case of malignant hyperthermia complicated by generalized compartment syndrome and rhabdomyolysis.
A healthy 21-year-old male who had previously been anaesthetized without complications underwent a laparotomy following a skiing accident. He developed severe malignant hyperthermia. The initial reaction was successfully treated with dantrolene, but during the following days the patient developed several compartment syndromes requiring fasciotomies. The patient died of hyperkalaemia in spite of continuous dialysis. We present a detailed description of the case and also discuss the role of propofol and rhabdomyolysis.


BCS-BEC crossover in a two-dimensional Fermi gas.
We investigate the crossover from Bardeen-Cooper-Schrieffer (BCS) superfluidity to Bose-Einstein condensation (BEC) in a two-dimensional Fermi gas at T=0 using the fixed-node diffusion Monte Carlo method. We calculate the equation of state and the gap parameter as a function of the interaction strength, observing large deviations compared to mean-field predictions. In the BEC regime our results show the important role of dimer-dimer and atom-dimer interaction effects that are completely neglected in the mean-field picture. Results on Tan's contact parameter associated with short-range physics are also reported along the BCS-BEC crossover.


Portable, battery-operated, low-cost, bright field and fluorescence microscope.
This study describes the design and evaluation of a portable bright-field and fluorescence microscope that can be manufactured for $240 USD. The microscope uses a battery-operated LED-based flashlight as the light source and achieves a resolution of 0.8 microm at 1000x magnification in fluorescence mode. We tested the diagnostic capability of this new instrument to identify infections caused by the human pathogen, Mycobacterium tuberculosis. Sixty-four direct, decontaminated, and serially diluted smears were prepared from sputa obtained from 19 patients suspected to have M. tuberculosis infection. Slides were stained with auramine orange and evaluated as being positive or negative for M. tuberculosis with both the new portable fluorescence microscope and a laboratory grade fluorescence microscope. Concordant results were obtained in 98.4% of cases. This highly portable, low cost, fluorescence microscope may be a useful diagnostic tool to expand the availability of M. tuberculosis testing at the point-of-care in low resource settings.


Clinical indicators for common paediatric conditions: Processes, provenance and products of the CareTrack Kids study.
In order to determine the extent to which care delivered to children is appropriate (in line with evidence-based care and/or clinical practice guidelines (CPGs)) in Australia, we developed a set of clinical indicators for 21 common paediatric medical conditions for use across a range of primary, secondary and tertiary healthcare practice facilities. Clinical indicators were extracted from recommendations found through systematic searches of national and international guidelines, and formatted with explicit criteria for inclusion, exclusion, time frame and setting. Experts reviewed the indicators using a multi-round modified Delphi process and collaborative online wiki to develop consensus on what constituted appropriate care. From 121 clinical practice guidelines, 1098 recommendations were used to draft 451 proposed appropriateness indicators. In total, 61 experts (n = 24 internal reviewers, n = 37 external reviewers) reviewed these indicators over 40 weeks. A final set of 234 indicators resulted, from which 597 indicator items were derived suitable for medical record audit. Most indicator items were geared towards capturing information about under-use in healthcare (n = 551, 92%) across emergency department (n = 457, 77%), hospital (n = 450, 75%) and general practice (n = 434, 73%) healthcare facilities, and based on consensus level recommendations (n = 451, 76%). The main reason for rejecting indicators was 'feasibility' (likely to be able to be used for determining compliance with 'appropriate care' from medical record audit). A set of indicators was developed for the appropriateness of care for 21 paediatric conditions. We describe the processes (methods), provenance (origins and evolution of indicators) and products (indicator characteristics) of creating clinical indicators within the context of Australian healthcare settings. Developing consensus on clinical appropriateness indicators using a Delphi approach and collaborative online wiki has methodological utility. The final indicator set can be used by clinicians and organisations to measure and reflect on their own practice.


Development and Internal Validation of a Multivariable Prediction Model for Adrenocortical-Carcinoma-Specific Mortality.
Adrenocortical carcinoma (ACC) has an incidence of about 1.0 per million per year. In general, survival of patients with ACC is limited. Predicting survival outcome at time of diagnosis is a clinical challenge. The aim of this study was to develop and internally validate a clinical prediction model for ACC-specific mortality. Data for this retrospective cohort study were obtained from the nine centers of the Dutch Adrenal Network (DAN). Patients who presented with ACC between 1 January 2004 and 31 October 2013 were included. We used multivariable Cox proportional hazards regression to compute the coefficients for the prediction model. Backward stepwise elimination was performed to derive a more parsimonious model. The performance of the initial prediction model was quantified by measures of model fit, discriminative ability, and calibration. We undertook an internal validation step to counteract the possible overfitting of our model. A total of 160 patients were included in the cohort. The median survival time was 35 months, and interquartile range (IQR) 50.7 months. The multivariable modeling yielded a prediction model that included age, modified European Network for the Study of Adrenal Tumors (mENSAT) stage, and radical resection. The c-statistic was 0.77 (95% Confidence Interval: 0.72, 0.81), indicating good predictive performance. We developed a clinical prediction model for ACC-specific mortality. ACC mortality can be estimated using a relatively simple clinical prediction model with good discriminative ability and calibration.


Gender Disparity in Inpatient Mortality After Transjugular Intrahepatic Portosystemic Shunt Creation in Patients Admitted With Hepatorenal Syndrome: A Nationwide Study.
The aim of this study was to evaluate inpatient mortality after transjugular intrahepatic portosystemic shunt (TIPS) creation compared with medical management (MM) in patients with hepatorenal syndrome (HRS). Patients with cirrhosis admitted with HRS between 2005 and 2014 were identified using associated International Classification of Diseases, Ninth Revision, codes in the National Inpatient Sample (n = 153,112). Non-TIPS candidates and patients with parenchymal renal disease were excluded (n = 73,454). The remaining admissions were assigned to groups of TIPS (International Classification of Diseases, Ninth Revision, code 39.1; n = 971) or MM (n = 78,687). Inpatient mortality was analyzed by treatment type and patient gender using χ2 tests. Logistic regression was performed to control for baseline differences in patient demographics, comorbid disease, and pretreatment mortality risk. Baseline patient demographics were similar. Patients treated medically had higher baseline disease severity (median mortality risk score, 8.3 with MM versus 6.1 with TIPS; P < .01). Inpatient mortality was strongly modified by patient gender. TIPS creation conferred inpatient mortality benefit in men (28% of the MM group versus 10% of the TIPS group, P < .01) independent of all covariates (odds ratio, 0.4; 95% confidence interval, 0.17-0.78; P < .01). Women treated with TIPS creation experienced no mortality benefit (29% MM versus 32% TIPS; odds ratio, 1.5; 95% confidence interval, 0.75-3.23; P = .23). TIPS creation is associated with reduced inpatient mortality in men, but not women, admitted with HRS. Drivers of this gender-based disparity are currently unclear and warrant focused investigation.


Inhalable dry powder product (DPP) of mRNA lipid nanoparticles (LNPs) for pulmonary delivery.
Pulmonary delivery of mRNA via inhalation is a very attractive approach for RNA-based therapy for treatment of lung diseases. In this work, we have demonstrated successful development of an mRNA-lipid nanoparticle (LNP) dry powder product (DPP), wherein the LNPs were spray dried using hydroalcoholic solvent along with mannitol and leucine as excipients. The desired critical attributes for the DPP were accomplished by varying the excipients, lipid composition, concentration of LNPs, and weight percentage of mRNA. Leucine alone or in combination with mannitol improved the formulation by increasing the mRNA yield as well as decreasing the particle size. Intratracheal administration of the DPP in mice resulted in luciferase expression in the trachea and lungs indicating successful delivery of functional mRNA. Our results show formulation optimization of mRNA LNPs administered in the form of DPP results in an efficacious functional delivery with great promise for future development of mRNA therapeutics for lung diseases.


Mechanical or inflammatory low back pain. What are the potential signs and symptoms?
Non-specific low back pain (NSLBP) is commonly conceptualised and managed as being inflammatory and/or mechanical in nature. This study was designed to identify common symptoms or signs that may allow discrimination between inflammatory low back pain (ILBP) and mechanical low back pain (MLBP). Experienced health professionals from five professions were surveyed using a questionnaire listing 27 signs/symptoms. Of 129 surveyed, 105 responded (81%). Morning pain on waking demonstrated high levels of agreement as an indicator of ILBP. Pain when lifting demonstrated high levels of agreement as an indicator of MLBP. Constant pain, pain that wakes, and stiffness after resting were generally considered as moderate indicators of ILBP, while intermittent pain during the day, pain that develops later in the day, pain on standing for a while, with lifting, bending forward a little, on trunk flexion or extension, doing a sit up, when driving long distances, getting out of a chair, and pain on repetitive bending, running, coughing or sneezing were all generally considered as moderate indicators of MLBP. This study identified two groups of factors that were generally considered as indicators of ILBP or MLBP. However, none of these factors were thought to strongly discriminate between ILBP and MLBP.


Automated measurement of distance-walked as a "sixth vital sign" for detecting infusion reactions during preclinical testing.
Infusion reactions are a major risk for advanced therapeutics (e.g., engineered proteins nanoparticles, etc.), which can trigger the complement cascade, anaphylaxis, and other life-threatening immune responses. However, during the early phases of development, it is uncommon to assess for infusion reactions, given the labor involved in measuring multiple physiological parameters in rodents. Therefore, we sought to develop an automated quantification of rodent locomotion to serve as a sensitive screening tool for infusion reactions, with minimal added labor-time for each experiment. Here we present the detailed methods for building a motion tracking cage for mice, requiring ∼$100 of materials, ∼2 h to build and set up completely, and employing freely available software (DeepLabCut). The distance-walked after injection was first shown to have the predicted effects for stimulants (caffeine), sedatives (ketamine), and toxins (lipopolysaccharide). Additionally, the distance-walked more sensitively detected the effects of these compounds than did pulse oximetry-based measurements of the classical vital signs of heart rate, respiratory rate, and blood oxygen saturation. Finally, we examined a nanomedicine formulation that has been in preclinical development, liposomes targeted to the cell adhesion molecule ICAM. While this formulation has been studied across dozens of publications, it has not previously been noted to produce an infusion reaction. However, the automated motion tracking cage showed that ICAM-liposomes markedly reduce the distance-walked, which we confirmed by measuring the other vital signs. Importantly, the motion tracking cage added < 5 min of labor time per 5-mouse condition, while pulse oximetry with a neck cuff (by far the most stable oximetry signal in mice) required ∼ 100 min of labor time. Thus, automated measurement of distance-walked can indeed serve as a "sixth vital sign" for detecting infusion reactions during preclinical testing. Additionally, the device to measure distance-walked is easy and cheap to build and requires negligible labor time for each experiment, enabling distance-walked to be recorded in nearly every infusion experiment.


Trends in lower-extremity amputations in people with and without diabetes in Spain, 2001-2008.
To examine trends in nontraumatic lower-extremity amputations (LEAs) over an 8-year period in patients with and without diabetes in Spain. We identified all patients who underwent an LEA using national hospital discharge data. Discharges were grouped by diabetes status: type 1 diabetes, type 2 diabetes, and no diabetes. The incidence of discharges attributed to amputations were calculated overall and stratified by diabetes status and year. We calculated length of stay and in-hospital fatality stratified by diabetes status and type of LEA. From 2001 to 2008, 46,536 minor LEAs and 43,528 major LEAs were performed. In patients with type 1 diabetes, the incidence of minor and major amputations decreased significantly from 2001 to 2008 (0.88-0.43 per 100,000 inhabitants and 0.59-0.22 per 100,000 inhabitants, respectively). In patients with type 2 diabetes, the incidence of minor and major LEAs increased significantly (9.23-10.9 per 100,000 inhabitants and 7.12-7.47 per 100,000 inhabitants). Hospital stay was similar among type 1 diabetic and type 2 diabetic subjects, according to the type of LEA. Only in-hospital mortality for minor LEAs among type 1 diabetic subjects decreased significantly (4.0% in 2001 vs. 1.6% in 2008). Our national data show a decrease in the incidence of major and minor LEAs in patients with type 1 diabetes and an increase among patients with type 2 diabetes. Further improvement is necessary in the preventive care and early treatment of patients with diabetes. The management of foot lesions, especially among type 2 diabetic patients, is particularly urgent.


[Pulmonary microembolism with particles of synthetic polymer "Polysorb"in the treatment of postpartum endometritis].
A case of fatal massive pulmonary microembolism with particles of the synthetic polymer preparation in a female of 26 early after delivery is reported. The case is interpreted as a maternal death of the 1st group due to occasional damage in the process of uterine cavity washing with a suspension of a synthetic polymer preparation polysorb in the treatment of purulent postpartum endometritis.


Mechanism of positive regulation by DsrA and RprA small noncoding RNAs: pairing increases translation and protects rpoS mRNA from degradation.
Small noncoding RNAs (sRNAs) regulate gene expression in Escherichia coli by base pairing with mRNAs and modulating translation and mRNA stability. The sRNAs DsrA and RprA stimulate the translation of the stress response transcription factor RpoS by base pairing with the 5' untranslated region of the rpoS mRNA. In the present study, we found that the rpoS mRNA was unstable in the absence of DsrA and RprA and that expression of these sRNAs increased both the accumulation and the half-life of the rpoS mRNA. Mutations in dsrA, rprA, or rpoS that disrupt the predicted pairing sequences and reduce translation of RpoS also destabilize the rpoS mRNA. We found that the rpoS mRNA accumulates in an RNase E mutant strain in the absence of sRNA expression and, therefore, is degraded by an RNase E-mediated mechanism. DsrA expression is required, however, for maximal translation even when rpoS mRNA is abundant. This suggests that DsrA protects rpoS mRNA from degradation by RNase E and that DsrA has a further activity in stimulating RpoS protein synthesis. rpoS mRNA is subject to degradation by an additional pathway, mediated by RNase III, which, in contrast to the RNase E-mediated pathway, occurs in the presence and absence of DsrA or RprA. rpoS mRNA and RpoS protein levels are increased in an RNase III mutant strain with or without the sRNAs, suggesting that the role of RNase III in this context is to reduce the translation of RpoS even when the sRNAs are acting to stimulate translation.


Anionic and cationic Hofmeister effects are non-additive for guanidinium salts.
To understand specific ion effects on a molecular level we explore the effect of salts on the rotational mobility of a model amide using dielectric spectroscopy. Based on our previous studies on the effect of strong denaturing anions or cations, here we study the additivity of the anionic and cationic effect. Using salts consisting of denaturing spherical anions and spherical cations we find such salts to affect the amide according to what one expects based on the additive activity of the individual ions. The guanidinium (Gdm+) cation appears to be a notable exception, as our results suggest that GdmI (and accordingly GdmSCN) is less efficient in hindering the rotation of the amide than KI or GdmCl.


CRP identifies homeostatic immune oscillations in cancer patients: a potential treatment targeting tool?
The search for a suitable biomarker which indicates immune system responses in cancer patients has been long and arduous, but a widely known biomarker has emerged as a potential candidate for this purpose. C-Reactive Protein (CRP) is an acute-phase plasma protein that can be used as a marker for activation of the immune system. The short plasma half-life and relatively robust and reliable response to inflammation, make CRP an ideal candidate marker for inflammation. The high- sensitivity test for CRP, termed Low-Reactive Protein (LRP, L-CRP or hs-CRP), measures very low levels of CRP more accurately, and is even more reliable than standard CRP for this purpose. Usually, static sampling of CRP has been used for clinical studies and these can predict disease presence or recurrence, notably for a number of cancers. We have used frequent serial L-CRP measurements across three clinical laboratories in two countries and for different advanced cancers, and have demonstrated similar, repeatable observations of a cyclical variation in CRP levels in these patients. We hypothesise that these L-CRP oscillations are part of a homeostatic immune response to advanced malignancy and have some preliminary data linking the timing of therapy to treatment success. This article reviews CRP, shows some of our data and advances the reasoning for the hypothesis that explains the CRP cycles in terms of homeostatic immune regulatory cycles. This knowledge might also open the way for improved timing of treatment(s) for improved clinical efficacy.


Exposure of ELF-EMF and RF-EMF Increase the Rate of Glucose Transport and TCA Cycle in Budding Yeast.
In this study, we investigated the transcriptional response to 50 Hz extremely low frequency electromagnetic field (ELF-EMF) and 2.0 GHz radio frequency electromagnetic field (RF-EMF) exposure by Illumina sequencing technology using budding yeast as the model organism. The transcription levels of 28 genes were upregulated and those of four genes were downregulated under ELF-EMF exposure, while the transcription levels of 29 genes were upregulated and those of 24 genes were downregulated under RF-EMF exposure. After validation by reverse transcription quantitative polymerase chain reaction (RT-qPCR), a concordant direction of change both in differential gene expression (DGE) and RT-qPCR was demonstrated for nine genes under ELF-EMF exposure and for 10 genes under RF-EMF exposure. The RT-qPCR results revealed that ELF-EMF and RF-EMF exposure can upregulate the expression of genes involved in glucose transportation and the tricarboxylic acid (TCA) cycle, but not the glycolysis pathway. Energy metabolism is closely related with the cell response to environmental stress including EMF exposure. Our findings may throw light on the mechanism underlying the biological effects of EMF.


The Family Support Movement and Schizophrenia in India.
To review the evolution of family support movement for schizophrenia in India and to report perspectives of family caregivers who are running family support groups across the country in the backdrop of recent legislations in India. Family support movement started in the 1990s, mostly by family caregivers independently in multiple cities across the country. Apart from periodic support meetings, they have successfully influenced recent legislations to address the felt needs of families. Mental health professionals need to gain skills to work collaboratively with assertive family caregivers to develop services to support those diagnosed with mental illness. Though there is a need for such movement, funding is poor and very few caregivers of persons with schizophrenia are forthcoming to participate. The formation of national federation with government and non-government partnership could help give the required impetus to the family support movement for persons with schizophrenia in India.


Responses of Ottelia alismoides, an aquatic plant with three CCMs, to variable CO2 and light.
Ottelia alismoides is a constitutive C4 plant and bicarbonate user, and has facultative crassulacean acid metabolism (CAM) at low CO2. Acclimation to a factorial combination of light and CO2 showed that the ratio of phosphoenolpyruvate carboxylase (PEPC) to ribulose-bisphosphate carboxylase/oxygenase (Rubisco) (>5) is in the range of that of C4 plants. This and short-term response experiments showed that the activity of PEPC and pyruvate phosphate dikinase (PPDK) was high even at the end of the night, consistent with night-time acid accumulation and daytime carbon fixation. The diel acidity change was maximal at high light and low CO2 at 17-25 µequiv g-1 FW. Decarboxylation proceeded at ~2-3 µequiv g-1 FW h-1, starting at the beginning of the photoperiod, but did not occur at high CO2; the rate was greater at high, compared with low light. There was an inverse relationship between starch formation and acidity loss. Acidity changes account for up to 21% of starch production and stimulate early morning photosynthesis, but night-time accumulation of acid traps <6% of respiratory carbon release. Ottelia alismoides is the only known species to operate CAM and C4 in the same tissue, and one of only two known aquatic species to operate CAM and bicarbonate use.


Interferon-gamma elevates nicotinamide N-methyltransferase activity and nicotinamide level in human glioma cells.
Nicotinamide N-methyltransferase (NNMT) catalyzes the N-methylation of nicotinamide. NNMT is strongly expressed in tumor cells and an increase in NNMT activity may reduce cellular nicotinamide level and thereby promote cell survival in the cells. However, there has been no report of a relationship between NNMT activity and nicotinamide level in tumor cells. We report herein that human glioma cells produce relatively large amounts of NNMT and that when these cells are cultured in the presence of interferon-gamma (IFN-gamma) their 1-methylnicotinamide levels increase. To clarify the mechanisms by which IFN-gamma increases 1-methylnicotinamide levels in these cells, we measured NNMT activity and the levels of NNMT expression, nicotinamide and nicotinamide adenine dinucleotide (NAD(+)) in the presence and absence of IFN-gamma. We also examined whether addition of exogenous 1-methylnicotinamide directly affects cell viability and/or the cellular levels of 1-methylnicotinamide, nicotinamide and NAD(+). While addition of 1-methylnicotinamide increased the total amount of cellular 1-methylnicotinamide present, it did not affect nicotinamide or NAD(+) levels, or cell viability. Conversely, IFN-gamma significantly increased NNMT activity and the nicotinamide cellular concentration, while leaving NNMT expression and the NAD(+) cellular concentration unchanged. Therefore, the increase in the 1-methylnicotinamide level found when IFN-gamma is present in culture may be a consequence of increases in both the nicotinamide concentration and NNMT activity, whereas, 1-methylnicotinamide did not influence nicotinamide levels, NAD(+) levels, or cell viability per se. These results suggest that an increase in NNMT activity does not always reduce cellular nicotinamide concentration in tumor cells.


Flagellin a toll-like receptor 5 agonist as an adjuvant in chicken vaccines.
Chicken raised under commercial conditions are vulnerable to environmental exposure to a number of pathogens. Therefore, regular vaccination of the flock is an absolute requirement to prevent the occurrence of infectious diseases. To combat infectious diseases, vaccines require inclusion of effective adjuvants that promote enhanced protection and do not cause any undesired adverse reaction when administered to birds along with the vaccine. With this perspective in mind, there is an increased need for effective better vaccine adjuvants. Efforts are being made to enhance vaccine efficacy by the use of suitable adjuvants, particularly Toll-like receptor (TLR)-based adjuvants. TLRs are among the types of pattern recognition receptors (PRRs) that recognize conserved pathogen molecules. A number of studies have documented the effectiveness of flagellin as an adjuvant as well as its ability to promote cytokine production by a range of innate immune cells. This minireview summarizes our current understanding of flagellin action, its role in inducing cytokine response in chicken cells, and the potential use of flagellin as well as its combination with other TLR ligands as an adjuvant in chicken vaccines.


The Lipid Research Clinics Coronary Primary Prevention Trial results. I. Reduction in incidence of coronary heart disease.
The Lipid Research Clinics Coronary Primary Prevention Trial (LRC-CPPT), a multicenter, randomized, double-blind study, tested the efficacy of cholesterol lowering in reducing risk of coronary heart disease (CHD) in 3,806 asymptomatic middle-aged men with primary hypercholesterolemia (type II hyperlipoproteinemia). The treatment group received the bile acid sequestrant cholestyramine resin and the control group received a placebo for an average of 7.4 years. Both groups followed a moderate cholesterol-lowering diet. The cholestyramine group experienced average plasma total and low-density lipoprotein cholesterol (LDL-C) reductions of 13.4% and 20.3%, respectively, which were 8.5% and 12.6% greater reductions than those obtained in the placebo group. The cholestyramine group experienced a 19% reduction in risk (p less than .05) of the primary end point--definite CHD death and/or definite nonfatal myocardial infarction--reflecting a 24% reduction in definite CHD death and a 19% reduction in nonfatal myocardial infarction. The cumulative seven-year incidence of the primary end point was 7% in the cholestyramine group v 8.6% in the placebo group. In addition, the incidence rates for new positive exercise tests, angina, and coronary bypass surgery were reduced by 25%, 20%, and 21%, respectively, in the cholestyramine group. The risk of death from all causes was only slightly and not significantly reduced in the cholestyramine group. The magnitude of this decrease (7%) was less than for CHD end points because of a greater number of violent and accidental deaths in the cholestyramine group. The LRC-CPPT findings show that reducing total cholesterol by lowering LDL-C levels can diminish the incidence of CHD morbidity and mortality in men at high risk for CHD because of raised LDL-C levels. This clinical trial provides strong evidence for a causal role for these lipids in the pathogenesis of CHD.


Rat hepatic mRNA-S14 and lipogenic enzymes during weaning: role of S14 in lipogenesis.
The rapid and marked response of hepatic mRNA-S14 sequence to both triiodothyronine and carbohydrate intake has made this sequence an attractive model for studying the action of hormonal and dietary factors. Because it is highly expressed and regulated only in lipogenic tissues, we have suggested that it plays a role in some aspect of lipid synthesis, transport, or metabolism. To provide more precise information regarding the function of S14 we have measured lipogenesis, lipogenic enzymes, beta-oxidation, and mRNA-S14 levels in spontaneously weaning neonatal rats and in rats prematurely weaned to a laboratory diet on postnatal day 17. After birth, the levels of lipogenesis, mRNA-S14, and the lipogenic enzymes malic enzyme (ME) and fatty acid synthase (FAS) were almost undetectable but increased with the onset of spontaneous weaning. Coincident with these changes, beta-oxidation decreased. Premature weaning beginning on day 17 resulted in an earlier and even more marked increase in lipogenesis, ME, FAS, and mRNA-S14. On day 19, ME and FAS activities were 6- to 19-fold more than activities in control suckling pups, whereas mRNA-S14 levels had risen to greater than 100 times the control values. Thus directional shifts in mRNA-S14 corresponded with indices of lipogenesis and were opposite to indices reflecting beta-oxidation. The response of mRNA-S14 therefore suggests that it may be related to the synthesis of fatty acids. On the other hand, the level of lipogenesis in the fetus was high despite the fact that the levels of both mRNA-S14 and ME were low. This dissociation raises the possibility that the S14 protein participates in lipogenesis in the neonate and adult but not in the fetus.


Strain differences in purified rat hepatic 3 alpha-hydroxysteroid UDP-glucuronosyltransferase.
Qualitative and quantitative differences of purified hepatic 3 alpha-hydroxysteroid UDP-glucuronosyltransferase were investigated in Wistar and Sprague-Dawley rats. Individual differences in the glucuronidation rate of androsterone and chenodeoxycholic acid were observed in hepatic microsomal fractions from Wistar but not Sprague-Dawley rats. No individual variation was observed in the glucuronidation of testosterone, p-nitrophenol or oestrone. The 3 alpha-hydroxysteroid UDP-glucuronosyltransferases from livers of Wistar and Sprague-Dawley rats were isolated and highly purified by using Chromatofocusing and affinity chromatography. The amount of 3 alpha-hydroxysteroid UDP-glucuronosyltransferase in the liver of Wistar rats exhibiting low rates for androsterone glucuronidation is about 10% or less than that found in hepatic microsomal fractions obtained from Wistar rats having high rates for androsterone glucuronidation. The apparent Km for androsterone with purified 3 alpha-hydroxysteroid UDP-glucuronosyltransferase from Wistar rats with high glucuronidation activity (6 microM) was not different from that observed for the enzyme purified from Sprague-Dawley animals, whereas that for the enzyme purified from Wistar rats with low glucuronidation activity was substantially higher (120 microM). Despite the differences in apparent Km values for androsterone, the apparent Km for UDP-glucuronic acid (0.3 mM) was not different in the different populations of rats.


Upregulation of E3 Ubiquitin Ligase CBLC Enhances EGFR Dysregulation and Signaling in Lung Adenocarcinoma.
CBLC (CBL proto-oncogene c) belongs to the CBL protein family, which has E3 ubiquitin ligase activity toward activated receptor tyrosine kinases. CBLC is frequently upregulated in non-small cell lung cancer (NSCLC), yet very little is known about the functions of CBLC in tumorigenesis. Here we show that CBLC is an epigenetically demethylated target and its expression can be upregulated in NSCLC after treatment with the DNA methylation inhibitor 5'-azacytidine. Depletion of CBLC significantly inhibited cell viability and clonogenicity in vitro and reduced tumor growth in a xenograft model. CBLC silencing further sensitized EGFR-mutated NSCLC cells to treatment with tyrosine kinase inhibitors. Conversely, ectopic expression of CBLC enhanced the activation of EGFR and downstream ERK1/2 signaling after ligand stimulation by competing with CBL for EGFR binding. Analysis of ubiquitin linkages on activated EGFR (aEGFR) revealed that CBLC ubiquitinated and positively regulated aEGFR stability through the conjugation of polyubiquitin by K6 and K11 linkages. This CBLC-mediated polyubiquitination promoted either preferential recycling of aEGFR back to the plasma membrane or trafficking to the cell nucleus. IHC analyses revealed a positive correlation between phospho-EGFR and CBLC in lung adenocarcinoma. In summary, we demonstrate a novel mechanism by which aEGFR escapes lysosomal degradation in a CBLC/ubiquitin-dependent manner to sustain its activation. Our work identifies CBLC as a potential diagnostic biomarker and also points to its utilization as a novel therapeutic target for NSCLC therapy.Significance: This work demonstrates the role of CBLC expression as a diagnostic biomarker and potential therapeutic target in lung adenocarcinoma. Cancer Res; 78(17); 4984-96. ©2018 AACR.


Histones activate the NLRP3 inflammasome in Kupffer cells during sterile inflammatory liver injury.
Cellular processes that drive sterile inflammatory injury after hepatic ischemia/reperfusion (I/R) injury are not completely understood. Activation of the inflammasome plays a key role in response to invading intracellular pathogens, but mounting evidence suggests that it also plays a role in inflammation driven by endogenous danger-associate molecular pattern molecules released after ischemic injury. The nucleotide-binding domain, leucine-rich repeat containing protein 3 (NLRP3) inflammasome is one such process, and the mechanism by which its activation results in damage and inflammatory responses following liver I/R is unknown. In this article, we report that both NLRP3 and its downstream target caspase-1 are activated during I/R and are essential for hepatic I/R injury, because both NLRP3 and caspase-1 knockout mice are protected from injury. Furthermore, inflammasome-mediated injury is dependent on caspase-1 expression in liver nonparenchymal cells. Although upstream signals that activate the inflammasome during ischemic injury are not well characterized, we show that endogenous extracellular histones activate the NLRP3 inflammasome during liver I/R through TLR9. This occurs through TLR9-dependent generation of reactive oxygen species. This mechanism is operant in resident liver Kupffer cells, which drive innate immune responses after I/R injury by recruiting additional cell types, including neutrophils and inflammatory monocytes. These novel findings illustrate a new mechanism by which extracellular histones and activation of NLRP3 inflammasome contribute to liver damage and the activation of innate immunity during sterile inflammation.


Gene expression profiles of immune mediators and histopathological findings in animal models of leptospirosis: comparison between susceptible hamsters and resistant mice.
Leptospirosis is a widespread zoonosis characterized by multiple organ failure and variable host susceptibility toward pathogenic Leptospira strains. In this study, we put the role of inflammatory mediators in parallel with bacterial burdens and organ lesions by comparing a susceptible animal model, the hamster, and a resistant one, the Oncins France 1 (OF1) mouse, both infected with virulent Leptospira interrogans serovar Icterohaemorrhagiae strain Verdun. Histological observations evidenced edema, congestion, hemorrhage, and inflammatory infiltration in the organs of hamsters, in contrast to limited changes in mice. Using reverse transcription-quantitative PCR techniques, we showed that the relative Leptospira burden progressively increased in hamster tissues, while a rapid clearance was observed in mouse tissues. The early regulation of the proinflammatory mediators interleukin-1β (IL-1β), IL-6, tumor necrosis factor alpha, and cyclo-oxygenase-2 and the chemokines gamma interferon-inducible protein 10 kDa/CXCL10 and macrophage inflammatory protein-1α/CCL3 in mouse tissues contrasted with their delayed and massive overexpression in hamster tissues. Conversely, the induction of the anti-inflammatory cytokine IL-10 was faster in the resistant than in the susceptible animal model. The role of these cytokines in the pathophysiology of leptospirosis and the implications of their differential regulation in the development of this disease are discussed.


Electronic structure and photoabsorption of Ti3+ ions in reduced anatase and rutile TiO2.
We have used two-photon photoemission (2PPE) spectroscopy and first-principles density functional theory calculations to investigate the electronic structure and photoabsorption of the reduced anatase TiO2(101) and rutile TiO2(110) surfaces. 2PPE measurements on anatase (101) show an excited resonance induced by reduced Ti3+ species centered around 2.5 eV above the Fermi level (EF). While this state is similar to that observed on the rutile (110) surface, the intensity of the 2PPE peak is much weaker. The computed oscillator strengths of the transitions from the occupied gap states to the empty states in the conduction band show peaks between 2.0 and 3.0 eV above the conduction band minimum (CBM) on both surfaces, confirming the presence of empty Ti3+ resonances at these energies. Although the crystal field environment of Ti ions is octahedral in both rutile and anatase, Ti3+ ions exhibit distinct d orbital splittings due to different distortions of the TiO6 units. This affects the directions of the transition dipoles from the gap states to the conduction band, explaining the polarization dependence of the 2PPE signal in the two materials. Our results also show that the Ti3+ induced states in the band gap are shallower in anatase than in rutile. The d → d transitions from the occupied gap states to the empty Ti3+ excited states in anatase can occur at energies well below 3 eV, consistent with the observed visible-light photocatalytic activity of Ti3+ self-doped anatase.


An interleukin-18 polymorphism is associated with reduced serum concentrations and better physical functioning in older people.
The proinflammatory cytokine interleukin-18 (IL-18) is associated with major disabling conditions, although whether as byproduct or driver is unclear. The role of common variation in the IL-18 gene on serum concentrations and functioning in old age is unknown. We used 1671 participants aged 65-80 years from two studies: the InCHIANTI study and wave 6 of the Iowa-Established Populations for Epidemiological Study of the Elderly (EPESE). We tested three common polymorphisms against IL-18 concentration and measures of functioning. In the InCHIANTI study, a 1 standard deviation increase in serum IL-18 concentrations was associated with an increased chance of being in the 20% of slowest walkers (odds ratio 1.45; 95% confidence interval, 1.17-1.80; p =.0007) and 20% of those with poorest function based on the Short Physical Performance Battery Score (odds ratio 1.52; 95% confidence interval, 1.22-1.89; p =.00016) in age sex adjusted logistic regression models. There was no association with Activities of Daily Living (p =.26) or Mini-Mental State Examination score (p =.66). The C allele of the IL-18 polymorphism rs5744256 reduced serum concentrations of IL-18 by 39 pmol/mL per allele (p =.00001). The rs5744256 single nucleotide polymorphism was also associated with shorter walk times in InCHIANTI (n = 662, p =.016) and Iowa-EPESE (n = 995, p =.026). In pooled ranked models rs5744256 was also associated with higher SPPB scores (n = 1671, p =.019). Instead of adjusting for confounders in the IL-18 walk time association, we used rs5744256 in a Mendelian randomization analysis: The association remained in instrumental variable models (p =.021). IL-18 concentrations are associated with physical function in 65- to 80-year-olds. A polymorphism in the IL-18 gene alters IL-18 concentrations and is associated with an improvement in walk speed. IL-18 may play an active role in age-related functional impairment, but these findings need independent replication.


Group and individual treatment strategies for distress in cancer patients.
Many cancer patients experience distress during the course of their illness. Recently, the National Comprehensive Cancer Network recommended that all cancer patients receive evaluation and treatment of distress as a routine part of their care. For some patients, psychosocial interventions may be helpful, but which patients benefit from what type of psychosocial interventions is unclear. To highlight the importance of this problem, this article examines the prevalence of distress in cancer patients and reviews the evidence that supports that cancer patients benefit from group and individual treatment strategies. Several randomized studies have examined the effects of group or individual therapy on both the emotional and the physiological well-being of cancer patients. Both individual and group interventions that are structured have proved effective in reducing distress. Clearly, more investigation is warranted and future research is needed to advance the understanding of structured interventions, to examine support groups, and to tailor psychological interventions to meet individual needs of distressed cancer patients.


An organoleptic survey of meads made with lactic acid-producing yeasts.
We previously reported the isolation a suite of wild lactic acid-producing yeasts (LAYs) that enable "primary souring" during beer fermentation without the use of lactic acid bacteria. With sour meads gaining popularity in modern mead making, we were interested in exploring the same primary souring approach to traditional semi-sweet meads. In this study, we utilized 13 LAY strains to produce semi-sweet meads using a standardized batch of honey must to ensure consistent starting conditions. Thirteen 11-L batches of mead were prepared, and each was inoculated with one of the LAY strains, along with two control batches inoculated with champagne yeast. The initial pH and specific gravity were measured for each batch before inoculation. Traditional organic staggered nutrient addition was utilized for the first 72 h of fermentation with specific gravities being taken throughout the mead making process. Meads were racked, tasted, stabilized, cold crashed, bottled, and transported to the American Mead Maker's Association 2018 Conference in Broomfield, Colorado. There, organoleptic surveys were conducted on these meads utilizing an array of tasters with varying levels of mead sensory analysis experience. The results of the sensory analysis, focusing on aroma and flavor, are discussed.


Delayed onset of severe hepatitis C-related liver damage following liver transplantation: a matter of concern?
Although histological hepatitis occurs in the majority of hepatitis C virus (HCV)-infected liver transplant recipients, the natural history is highly variable. Whereas progression to cirrhosis occurs in up to 30% after 3 to 7 years, the disease remains stable in another third of patients, in whom protocol liver biopsies might be avoided. However, there is recent concern that with prolonged follow-up, some patients with initial benign recurrence may develop a late-onset aggressive course. Aims of the study are to determine the incidence and factors associated with this event. Based on yearly protocol biopsies (median, five biopsies; range, three to seven biopsies), we evaluated the histological outcome of 57 HCV type 1b-infected transplant recipients with initial benign recurrence, defined as stable histological state (fibrosis stage F0 or F1) during the first 3 years posttransplantation. Severe late-onset liver damage is defined as progression to F3 or F4 in patients with previous benign recurrence. Potential predictors of this event include demographics, donor-related factors, liver enzyme levels at 1 and 3 (or baseline) years posttransplantation, activity grade and fibrosis stage at 1 and 3 years posttransplantation, nonalcoholic steatohepatitis-related variables occurring within the first 3 years posttransplantation (diabetes, hyperlipidemia, obesity), use of some drugs (renin-angiotensin inhibitors, ursodeoxycholic acid), and the advent of any unusual event. The incidence of severe late-onset liver damage was 35% (n = 20). Twelve transplant recipients progressed to F3, whereas 8 transplant recipients progressed to F4. Sudden histological deterioration was observed on postoperative biopsy 5 in 12 patients; biopsy 6 or 7, in 7 patients; and biopsy 4, in 1 patient. Variables associated with this event in univariate analysis were fibrosis stage and activity grade (and its components) at baseline (P <.0001), recipient female gender (P =.04), alanine aminotransferase (ALT) level at 1 year posttransplantation (P =.02), and aspartate aminotransferase (AST) and ALT levels at baseline (P =.008 and P =.005, respectively). By multivariate analysis, only one variable was retained in the model: fibrosis stage at baseline (relative risk, 11; 95% confidence interval, 3 to 41; P =.0007), whereas AST level almost reached statistical significance (P =.07). In conclusion, delayed HCV-related severe liver damage is not infrequent in transplant recipients with initial benign recurrence, occurring in approximately one third of them. The presence of some degree of fibrosis at baseline appears to predict this sudden change in the natural history of recurrent hepatitis C. Based on these findings, we recommend continuing protocol biopsies and evaluating potential antiviral therapy in transplant recipients with evidence of some fibrosis (even if it is only portal).


Establishing a method of vector contamination identification in database sequences.
The nucleotide sequence databases are invaluable tools both for the private and the academic research communities, from the retrieval of sequences to homology searching. Several issues related to data quality, such as the existence of sequencing artifacts and errors, are facing the databases. We investigated a major source of these errors, i.e. the presence of vector-contaminated sequences. Using a panel of 180 vector polylinker sequences, we found 0.36% or 3029 vector-matching sequences in GenBank Release 95-96, with an average vector-matching length of 72 nucleotides. The number of vector-contaminated sequences has been growing with the database; however, the percent contamination has remained approximately constant at an average of 0.28% from 1982 to 1996. Access to the database of vector polylinker sequences via sequence similarity searching is available at http://seqsim.ncgr.org/vector/ firstname.lastname@example.com


Phenylcinnamides as novel antimitotic agents.
Compound 8H is a phenylcinnamide that induces G2/M-phase cell cycle arrest and cell death in cancer cell lines. Here we show that 8H exerts its cytotoxic activity through disruption of microtubule dynamics in vitro and in cell culture. A series of cinnamide derivatives were synthesized and evaluated, and several new compounds were identified that improve on the activity of the parent compound, with IC(50) values for induction of cell death ranging from 1 to 10 microM. Notably, these compounds retain potency in the HL-60/VCR leukemia cell line, which is resistant to antimitotic cancer drugs vincrisitine and paclitaxel through up-regulation of P-glycoprotein drug efflux pumps. As P-glycoprotein expression is often responsible for drug resistance in cancer and the exclusion of compounds from the central nervous system, 8H and its derivatives merit further examination as potential antimitotic therapeutics, specifically for brain cancers and cancers that are resistant to standard antimitotic agents.